The present invention generally relates to 1) compositions that are used orally in treating the clinical condition known as xerostomia, that increase salivation, alleviate dry mouth and the sensations of dry mouth, and thereby aid in maintaining or improving oral hygiene, and methods of using same; 2) compositions that cause local oral anesthesia by direct contact, thereby alleviating pain and dryness in the oral cavity and pharynx caused by dental conditions, cough, sore throat, radiotherapy, surgery and other treatments that may affect the oral cavity and methods of using same; 3) compositions that may be described as oral sensates, that produce sensations of tingling, numbness, moistness and other sensations, and methods of using same; 4) as a flavor enhancer and potentiator; 5) compositions that may include any potential combinations of effects as described above in 1, 2, 3, and 4, and methods of using same. More particularly, the invention relates to oral compositions that include an herbal extract that address a variety of oral conditions; produce a variety of oral sensations, and methods of using the same.
Heliopsis longipes S. F. Blake (Asteraceae) is a herbaceous plant species found in Mexico that has been disclosed over fifty years ago as having possible commercial value as a source of insecticide. Little, Jr., E. L., Heliopsis longipes, a Mexican insecticidal plant species, Journal of the Washington Academy of Sciences, Vol.38, No.8, pp.269-274 (Aug. 15, 1948). More particularly, the roots of Heliopsis longipes have been used in Mexico to make local insecticides. Id. This use of the plant was discontinued over four decades ago. While this was one use of Heliopsis longipes roots, these roots have been used primarily as a spice or flavoring, as chewing the root causes numbness and tingling in the mouth and tongue and stimulates salivation. Id. These roots were also chewed to relieve toothache. Id. One incident is reported of an adverse effect, when a great, but undisclosed, quantity of these roots was eaten. Id.
Extracts from the roots of Heliopsis longipes have been used in a few medical applications. Id. For example, reportedly, such an extract has been used for treating colds and pneumonia, and an alcoholic extract has been tested for use as an anesthetic for tooth extraction. Id. It has also been reported that an extract of these roots possesses antiseptic properties. Molina-Torres, J., et al., Antimicrobial properties of alkamides present in flavouring plants traditionally used in Mesoamerica: affinin and capsaicin, Journal of Ethnopharmocology, Vol.64, Iss.3, pp.241-248 (March 1999). A crude methanol extract of Heliopsis longipes roots has been described as having the potential to generate anti-infective agents, although this extract reportedly does not show any activity in plate diffusion tests against either E. coli (Gram negative bacteria) or B. subtilis (Gram positive bacteria). Id.; and Gutierrez-Lugo, M. T., et al., Antimicrobial and cytotoxic activities of some crude drug extracts from Mexican Medicinal plants, phytomedicine, Vol.2 (4), pp.341-347 (1996). An ethanol extract of Heliopsis longipes roots has been reported as having variable bactericidal effects on E. coli and S. aureus. Romero-R., C. M., et al., Preliminary Studies of the Antibacterial, Insecticidal, and Toxicological Effects of Chiluan Root (Heliopsis Longipes), as translated, Veterinaria Mexico, pp. 151-156, (1989).
Heliopsis longipes roots are known to contain a bioactive alkamide, affinin, identified as N-isobutyl-2E, 6Z, 8E-decatrienamide or N-isobutyldeca-trans-2,cis-6,-trans-8-trienamide. Respectively, Id.; and Crombie, L., et al., Amides of Vegetable Origin. part X. The Stereochemistry and Synthesis of Affinin, Journal of Chemical Society, pp.4970-4976 (1963). Affinin has also been identified as N-isobutyl 2,6,8-decatrienoamide in one publication, in another publication, and N-isobutyldodeca-2-trans-6-cis-8-trans-trienamide in another publication. Respectively, Jacobson, M., et al., Correction of the Source of xe2x80x9cAffininxe2x80x9d (N-Isobutyl-2,6,8-Decatrienoamide, Journal of Organic Chemistry 12, pp.731-732 (1947) (emphasis added); and Ogura, M., et al., Ethnopharmacologic studies. I. Rapid solution to a problemxe2x80x94oral use of Heliopsis longipesxe2x80x94by means of a multidisciplinary approach, Journal of Ethnopharmacology, 5, pp.215-219 (1982) (emphasis added). Purified affinin, prepared from an ethanol extract of Heliopsis longipes roots, has been reported as being toxic to certain microorganisms, the toxicity varying for Gram positive and Gram negative bacteria. Molina-Torres, J., et al. An aqueous solution of affinin, prepared from a powder of an ethanol extract of Heliopsis longipes roots, has also been reported as having an analgesic effect when administered orally to mice at doses of from 2.5 to 10.0 mg/kg, with severe depression of normal motor activity and two out of five deaths occurring at the highest dose. Ogura, M., et al.
In the one publication where affinin is identified as N-isobutyl-dodeca-2-trans-6-cis-8-trans-trienamide, it was said to be identical with spilanthol, the pungent principle of several Spilanthes species. Ogura, M., et al. However, in the publication of Little, Jr., affinin is said to be similar to spilanthol, which has been isolated from flower heads of a species of Spilanthes. Little, Jr., E. L., at p.270. The flowers and leaves of Spilanthes acmella L. var. oleracea Clarke are reported as having been used as a spice and as a folk medicine for stammering, toothache, stomatitis and throat complaints. Ramsewak, R. S., et al., Bioactive N-isobutylamides from the flower buds of Spilanthes acmella, Phytochemistry 51, pp. 729-732 (1999).
1) The present invention provides compositions based on Heliopsis longipes root that are used orally in treating the clinical condition known as xerostomia, or more generally, dry mouth, that increase salivation, alleviating dry mouth and the sensations of dry mouth, and in maintaining or improving oral hygiene, and methods of using the same.
2) The present invention provides compositions based on Heliopsis longipes root that may provide some degree of local anesthesia and a sensation of numbness to all or portions of the oropharynx including teeth, gums, lips, tongue, palates, throat, and to the upper respiratory passageways such as the trachea, and bronchi. This provides some degree of relief from pain, dryness, irritation, and inflammation to these regions. There my be an improvement in swallowing that is impaired by illness and drying of the oropharynx. An anti-bacterial and anti-viral affect may also occur with reductions in bacterial and viral counts, and improvement from infections of these anatomical regions.
3) The present invention provides compositions based on Heliopsis longipes root that may cause desirable sensations to the same anatomical regions, these sensations consisting of tingling, numbness, moistness, acerbic taste, soothing, and other sensations.
4) The present invention provides compositions that may enhance other flavors, natural and artificial, and combinations of themxe2x80x94by increasing their strength and qualities, and by potentiating flavors in duration and quality.
The herbal composition includes an extract from Heliopsis longipes root in an amount sufficient to promote the above goals and an oral carrier for said extract. A suitable amount of the extract is from about 0.01 to about 10 weight percent of the overall composition. preferably, the extract is present in an amount sufficient to provide the above benefits for a prolonged period, i.e., for one minute or more.
A particular advantage of the inventive compositions is that they employ an extract of the Heliopsis longipes root, and thus, use a very small amount of the plant itself. This is especially important because the plant is believed to grow in a narrow geographic region, and thus, could become endangered if there were to be overly aggressive harvesting of wild plants. A horticultural project in the region has been started, to farm the plant and avoid any use of plant material from wild sources.
The compositions may be provided in oral formulations such as powders, gels, pastes, tablets, capsules, gums, lozenges, mints, candy, other confectionery materials, aerosols or sprays, fluids, rinses or mouthwashes, dentifrices, such as tooth-powders, tooth-gels, tooth-pastes, and extract-impregnated dental flosses, and the like. A particularly preferred composition is a gum with a solid exterior and a liquid center, wherein both the solid exterior and the liquid center contain an effective amount of the extract composition. A particular advantage of this composition is that the liquid center delivers the extract to the oral cavity quickly thus initiating salivation, while the solid gum delivers additional extract to the oral cavity over a prolonged period, a combination that provides a particularly effective treatment of the oral cavity for maintaining or improving oral hygiene by causing and increasing salivation.
Accordingly, it is a principal object of the invention to provide an herbal composition including an extract from Heliopsis longipes root in an amount effective to promote oral hygiene, and/or local anesthesia by contact, and/or a variety of desirable sensations to the same regions and to treat a wide variety of oral disorders, and unpleasant sensations.
It is an object of the invention to provide an herbal composition including an extract from the Heliopsis longipes root and an oral carrier in any one of a wide variety of forms; e.g., a powder, a gel, a paste, a tablet, a capsule, an oral film, a mouthwash, a gum, a candy, a confection, a lozenge, a liquid preparation such as a droplet dispenser, or aerosol dispenser, etc.
It is a further object of the invention to provide a method of treating an oral cavity with an herbal composition including a medicinally effective amount of an extract from the Heliopsis longipes root.
Further objects and advantages of the present invention will become readily apparent from a review of the following specification and claims.
The present invention provides herbal compositions, which include an extract of Heliopsis longipes root, that are formulated for oral use. Herein, the extract of Heliopsis longipes root may be called the extract, the Heliopsis longipes extract, the Heliopsis longipes root extract, and the like, where such terms have the same meaning. The compositions may be provided in oral formulations such as powders, gels, pastes, tablets, capsules, gums, lozenges, aerosols or sprays, fluids, rinses or mouthwashes, dentifrices, such as toothpowders, tooth gels, toothpastes, and extract-impregnated dental flosses, and the like. Regardless of the particular form of the compositions, the compositions include an extract of Heliopsis longipes root, as the active component, and a carrier for the extract that is suitable for oral use. When taken or administered orally, the compositions promote increased salivation and improve oral hygiene, and/or cause local anesthesia by contact, and/or a variety of desirable sensations. They may enhance and potentiate other flavorings used in commercial products.
As used herein, oral hygiene refers to acceptable or good health in terms of salivation, moistening of mouth and throat, freshness of breath, dental condition, gum condition, condition of oral mucosa, condition of an oral bio-film, condition of oral bacteria or oral plaque, and/or the like, as well as other specific conditions described herein. Further, as used herein, promoting refers to maintaining a condition of acceptable or good oral hygiene or improving a condition such that acceptable or good hygiene results. As used herein, local anesthesia by contact refers to a numbing and/or diminution of sensation to the tissues, which are in contact with the invention, particularly to a reduction in painful and uncomfortable sensations.
The Heliopsis longipes extract may be prepared using standard means or methods, such as by contacting the plant material with an appropriate solvent to prepare a botanical tincture, or by any other conventional means or method, such as by CO2 extraction, freeze-drying, spray-drying, and the like. (See Gennaro AR: Remington: The Science and Practice of Pharmacy, Mack Publishing Company, Easton Pa. 1995 and The United States Pharmacopeia 22nd rev, and The National Formulary (NF) 17 ed, USP Convention, Rockville Md., 1990.) The extract is prepared using a root or roots of Heliopsis longipes and a solvent, which may be water, such as distilled water, an aqueous solvent, such as water combined with other solvents, an organic solvent, such as hexane and glycerin, or an alcohol, such as ethanol, or any combination thereof. Preferably, an alcohol or a hydro-alcohol solvent is used, and most preferably, ethanol or a combination of ethanol and water is used.
The resulting extract is typically composed of a wet or liquid component that is light brown to golden in color and a dry or solid component, in amounts of about 90.0 to about 99.9 weight percent, such as about 98 weight percent, and about 10 to about 0.01 weight percent, such as about 2 weight percent, respectively, relative to the extract. The composition, including the extract in the wet-dry form just described, may be formulated as a liquid. Alternately, the composition may be formulated as a powder or paste, such as a powder including about 66.6 weight percent extract and 33.4 weight percent carrier on a wet basis; or about 0.01 to about 100 weight percent extract on a dry basis-including the natural product sprayed on itself, such as about 2 to 10 weight percent extract on a dry basis, or in any combination or permutation for either method-wet or dry.
It is important to note here that an affinin standard has been produced, for the first time enabling quantitative assay and standardization of dosage of the active ingredient from batch to batch of products.
According to one aspect of the invention, the extract component of the inventive composition is provided in an amount sufficient to promote oral hygiene, such as from about 0.5 mg to 1000 mg, preferably, from about 10 mg to about 200 mg, and most preferably, from about 10 mg to about 100 mg, per effective dose of the composition. A sufficient amount of the extract component is from about 0.1 to about 10 weight percent relative to the inventive composition. Generally, the liquid, powder, and paste formulations containing such an amount of the extract component are equally efficacious in promoting Treatment of xerostomia, alleviating dry mouth and promoting oral hygiene, causing local anesthesia, and desirable sensations in the oropharynx.
When the inventive composition is placed in a person""s mouth, the active extract component generates a characteristic acerbic, lemon- or citron-like taste, and the person will experience a strong, pleasant, tingling sensation in the mouth accompanied by salivation. Salivation is an important element in oral hygiene, as saliva tends to wash the mouth of food, and contaminants; promotes a balanced ecology of the oral cavity including the gums and teeth; and salivation refreshes the mouth. Thus, this property of stimulating the salivary glands makes the inventive composition useful and beneficial for oral and dental hygiene, and dental and oral clinical conditions, these including alleviating xerostomia and the sensations and perception of dry mouth; reducing oral bacteria, reducing dental caries, reducing halitosis, reducing peri-odontitis, reducing oral plaque, and promoting the healing of and alleviation of oral lesions, such as any lesion present in the mouth, a lesion induced by stomatitis, a lesion induced by herpes, and the like. Additionally, because of its local anesthetic effects, the inventive composition may reduce pain, sore throat, and suppress the cough reflex. It may improve swallowing by reducing dryness of the throat through increasing salivation and/or by producing a local anesthetic effect.